Maintenance of axo-oligodendroglial paranodal junctions requires DCC and netrin-1.
Paranodal axoglial junctions are essential for the segregation of myelinated axons into distinct domains and efficient conduction of action potentials. Here, we show that netrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNS myelin. We then address whether netrin-1 signaling influences paranodal adhesion between oligodendrocytes and axons. In the absence of netrin-1 or DCC function, oligodendroglial paranodes initially develop and mature normally but later become disorganized. Lack of DCC or netrin-1 resulted in detachment of paranodal loops from the axonal surface and the disappearance of transverse bands. Furthermore, the domain organization of myelin is compromised in the absence of netrin-1 signaling: K+ channels inappropriately invade the paranodal region, and the normally restricted paranodal distribution of Caspr expands longitudinally along the axon. Our findings identify an essential role for netrin-1 and DCC regulating the maintenance of axoglial junctions.
Jarjour
Andrew A
AA
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A2B4.
Bull
Sarah-Jane
SJ
Almasieh
Mohammadali
M
Rajasekharan
Sathyanath
S
Baker
K Adam
KA
Mui
Jeannie
J
Antel
Jack P
JP
Di Polo
Adriana
A
Kennedy
Timothy E
TE
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000075389:DCC Receptor; D017629:Gap Junctions / Q000502:physiology* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D000075388:Netrin-1; D009836:Oligodendroglia / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000502:physiology*; D012160:Retina / Q000378:metabolism / Q000637:transplantation; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000502:physiology*
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D000075389:DCC Receptor; C501912:Dcc protein, rat; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1